ITP: The Past Decade Ming Hou Qilu Hospital, Shandong University

Nomenclature Idiopathic Thrombocytopenic Purpura (ITP) Immune Thrombocytopenia (ITP) 2007 International ITP working group. Blood. 2009, 113(11):

Phases of ITP International ITP working group. Blood. 2009, 113(11): Months Chronic ITP Acute ITP Months 12 Months Newly ITPPersistent ITPChronic ITP

USA UK Japan Epidemiology and incidence of ITP France Danmark

Pathogenesis of ITP Decreased production Increased destruction Humoral immunity Cell immunity Spleen RES Liver Desialya tion CTL lysis Liver Desialya tion J Immunol Jun 15;194(12): Br J Haematol Apr;165(2): Loss of Immune tolerance Dysmegakaryocyt opoiesis Differe ntiation Aapop tosis

Loss of T cell tolerance Anergy T cell Tregs Apoptotic T cell Th1/Th2

T cell-mediated cytotoxicity

Dysmegakaryocytopoiesis

Desialyation Hepatocytes PLT Platelet desialylation Qiu J, ASH Annual Meeting Abstracts, 2014 Ni H, Nat Communication, 2015

Laboratory Diagnosis of ITP MAIPA/Flow Cytometric Immunobead Assay immune vs non-immune TPO concentration assay ITP vs atypical AA or MDS Curr Hematol Rep Mar;4(2): Br J Haematol Sep;146(6): Eur J Haematol Apr;86(4): Br J Haematol Jun;101(3):420-4.

Treatment not indicated platelet > 30×10 9 /L no bleeding symptom no increased risk of bleeding International ITP working group. Blood. 2009, 113(11): ITP therapy

Conventional PDN HD-DXM International ITP working group. Blood. 2009, 113(11): First-line treatment short-term application

Conventional PDN vs HD-DXM One or two courses of HD-DXM demonstrated higher CR rate, shorter time to response and less adverse events than PDN. Wei Y, et al, Conventional Oral Prednisone Versus High-Dose Dexamethasone for Management of Adult Immune Thrombocytopenia: A Prospective Randomized Multicenter Clinical Trial, 2014 ASH abstract, 1455 NCT

Thrombopoiesis stimulating agents rhTPO Romiplostim Eltrombopag short TTR low sustained response rate N Engl J Med. 2007; 357(22): Lancet. 2008;371(9610): Lancet. 2009;373(9664): N Engl J Med. 2010;363(20): Int J Hematol. 2012;96(2): Blood. 2015;125(10): Second-line treatment - 1

Rituximab long TTR high sustained response rate Blood. 2001;98(4): Ann Intern Med. 2007;146(1): Haematologica. 2008; 93(6): Blood. 2012;119(25): Blood. 2015;125(10): Lancet. 2015;385(9978): Second-line treatment - 2

Splenectomy 32% sustained response surgical risk post-splenectomy state Blood. 2004;104(9): Blood. 2013;121(23): Second-line treatment - 3

DXM plus Rituximab DXM plus Eltrombopag rhTPO plus Rituximab DXM, Rituximab and Cyclosporin Blood. 2015;125(10): Blood. 2010;115(14): David GA. ASH Annual Meeting Abstracts, 2013 Blood May 13. Epub ahead of print Combined therapy

Definition of response CR: platelet count > 100×10 9 /L and absence of bleeding R: platelet count > 30×10 9 /L and at least 2-fold increase the baseline count and absence of bleeding NR: platelet count < 30×10 9 /L or less than 2-fold increase of baseline

ITP: The Next Decade Restoration of immune tolerance Tregs/Bregs BAFF/BAFF-R antagonist MSC/Thalidomide MDSC DANA/Oseltamivir Anti-inflammatory macrophages/dasatinib

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